This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We will perform three independent 15 microseconds molecular dynamics simulations (45 microseconds total) of E. coli's chemotaxis signaling protein that translates extracellular signals into the cell and activates kinase complexes. Known mutations (equivalent to in vivo chemical modifications) can suppress ('locked-off') or hyper-activate ('locked-on') the wild-type protein's basal kinase activation. The accepted, but unproven, functional hypothesis is that mutations modify the protein's structure and dynamics. We will simulate the wild-type, locked-on (hyperactive) and locked-off (inactive) species for 15 microseconds each to characterize for the first time how variations in protein structure and dynamics control the initiation of the chemotactic signal.